The long-range objective of our work is to develop safe and effective drugs to prevent colon cancer, which is the fourth most common incident cancer in America with over 58,000 people dying of the disease in the year 2000. Our specific aims in this application are: 1.To conduct a randomized, double-blind placebo-controlled phase III clinical chemoprevention trial of the combination of DFMO plus sulindac to decrease the rate of new adenomatous polyp formation. 2. To correlate the effects of the combination on polyamine and prostaglandin contents in the flat mucosa to the rate of adenoma formation. 3. To determine the rate of side effects in patients randomized to the combination therapy over the course of the intervention. The major objectives of this investigation are to reduce the recurrence rate of adenomatous colonic polyps without producing toxicity greater than that seen in the placebo group. The overall goal of our work is to develop safe combinations of chemoprevention agents that can be used in the practice setting and complement current surveillance efforts.